Tetrahydrofuran → HCID 59736811, compound

HRID 252865Notes

Reaction equation

HRID 252865 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]2S[CH:10]=[CH:11][CH:12]=2)=[CH:4][C:3]=1[NH:13][C:14](=[O:34])/[CH:15]=[CH:16]/[C:17]1[CH:22]=[CH:21][C:20](NS(C2C=CC(C)=CC=2)(=O)=O)=CC=1.F[P-](F)(F)(F)(F)F.N1([O:51][P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C([Si](C)(C)[O:67][C:68]1C=CC(C2C=CC=CC=2)=CC=1N)(C)(C)C.C(N([CH2:88][CH3:89])CC)C.CCCC[N+:94]([CH2:103][CH2:104][CH2:105][CH3:106])([CH2:99]CCC)CCCC.[F-].C1[CH2:112][O:111][CH2:110][CH2:109]1>CN(C=O)C.[Na+].[Cl-]>[CH3:112][O:111][C:110]1[CH:109]=[C:103]([NH:94][CH2:99][C:22]2[CH:17]=[CH:16][C:15]([C:14]([NH:13][C:3]3[CH:4]=[C:5]([C:8]4[CH:12]=[CH:11][CH:10]=[CH:89][CH:88]=4)[CH:6]=[CH:7][C:2]=3[OH:51])=[O:34])=[CH:20][CH:21]=2)[CH:104]=[CH:105][C:106]=1[O:67][CH3:68]

Participants

9

Reactant 6

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2724141Tetrabutylammonium FluorideHCID 59736802HCID 59736802, compoundHCID 59736851HCID 59736851, compound

Product 1

HCID 59736811HCID 59736811, compound

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of acid 4 (scheme 1) (125 mg, 0.439 mmol) in DMF (3 mL) was added BOP (293 mg, 0.662 mmol). After stirring this solution for 10 minutes, aniline 311 (197 mg, 0.659 mmol) was added, along with triethylamine (0.31 mL, 2.22 mmol). The resulting solution was stirred at room temperature for 16 h prior to removal of the solvent, and dissolution of the residue in THF (5 mL). A solution of TBAF in THF (1.0 M, 0.66 mL, 0.659 mmol) was then added, and the reaction mixture was stirred at room temperature for 5 minutes, diluted with a saturated solution of NaCl (10 mL), and extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered and concentrated. After purification by flash chromatography (eluent 0-80% EtOAc in hexanes), the title compound 312 was obtained as a light yellow solid (82 mg, 41% yield). 1H NMR: (DMSO) δ (ppm): 3.62 (s, 3H), 3.69 (s, 3H), 4.34 (d, J=5.7 Hz, 2H), 6.03 (m, 2H), 6.35 (d, J=2.2 Hz, 1H), 6.68 (d, J=8.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 7.32 (t, J=7.2 Hz, 1H), 7.37 (dd, J=10.4, 1.6 Hz, 1H), 7.45 (t, J=7.6 Hz, 2H), 7.52 (d, J=8.0 Hz, 2H), 7.59 (d, J=7.6 Hz, 2H), 7.95 (d, J=8.0 Hz, 2H), 8.03 (br s. 1H), 9.58 (br s, 1H), 10.00 (br s, 1H). MS: (calc.) 454.5; (obt.) 455.4 (MH)+.

Workup

  1. stirringThe resulting solution was stirred at room temperature for 16 h
  2. customto removal of the solvent, and dissolution of the residue in THF (5 mL)
  3. stirringthe reaction mixture was stirred at room temperature for 5 minutes
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customAfter purification by flash chromatography (eluent 0-80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d94b19babad24971ba84f2413b05c808
Source dataset
uspto-grants-2011_01
Patent number
US07868205B2

Reaction notes

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